The Role of the Gut Microbiota in Coronary Heart Disease.

PURPOSE OF REVIEW: This review focuses on recent evidence examining the role gut microbiota play in coronary heart disease. It also provides a succinct overview of current and future therapies targeting the gut microbiota for coronary heart disease risk reduction. RECENT FINDINGS: A consensus has been reached that differences exist in the gut microbiotas of patients with coronary heart disease. Studies have shown that the gut microbiota is associated with obesity, diabetes, dyslipidemia, and hypertension, which are risk factors for coronary heart disease. The gut microbiota is involved in mediating basic metabolic processes, such as cholesterol metabolism, uric acid metabolism, oxidative stress, and inflammatory reactions, through its metabolites, which can induce the development of atherosclerosis and coronary heart disease. Interfering with the composition of gut microbiota, supplementing probiotics, and fecal donation are active areas of research to potentially prevent and treat coronary heart disease. Gut microbiota are causally associated with coronary heart disease. We analyzed the gut microbiota's effects on risk factors for coronary heart disease and studied the effects of gut microbiota metabolites on coronary heart disease. Gut microbiota is a potential target for preventing and treating coronary heart disease.

A comparison between the effects of flaxseed oil and fish oil supplementation on cardiovascular health in type 2 diabetic patients with coronary heart disease: A randomized, double-blinded, placebo-controlled trial.

This study compared the effects of flaxseed and fish oil supplementation on cardiovascular risk parameters in diabetic patients with coronary heart disease. Participants were randomly allocated into three intervention groups to receive either 1,000 mg of omega-3 fatty acids from fish oil or 1,000 mg of omega-3 fatty acids from flaxseed oil or placebo (n = 30 each group) twice a day for 12 weeks. A significant reduction in insulin levels (.04) was observed following flaxseed oil and fish oil supplementation compared with the placebo. In addition, a significant reduction in high-sensitivity C-reactive protein (.02) was seen after flaxseed oil supplementation compared with the placebo and a significant increase in total nitrite (.001) was seen after flaxseed oil and fish oil intake compared with placebo. Additionally, a significant increase in total antioxidant capacity (p < .001) after consuming flaxseed oil and fish oil compared with placebo and glutathione levels (.001) after consuming fish oil compared with flaxseed oil and placebo was observed. Overall, our study revealed the beneficial effects of flaxseed oil and fish oil supplementation on few metabolic profiles. This study suggests that the effect of flaxseed oil in reducing insulin and increasing total nitrite and total antioxidant capacity is similar to fish oil.

n-3 Fatty acids and risk for fatal coronary disease.

The purpose of this review is to consider the effects of the long-chain n-3 fatty acids found in marine foods, EPA and DHA, on risk for CVD, particularly fatal outcomes. It will examine both epidemiological and randomised controlled trial findings. The former studies usually examine associations between the dietary intake or the blood levels of EPA + DHA and CVD outcomes or, on occasion, total mortality. For example, our studies in the Framingham Heart Study and in the Women's Health Initiative Memory Study have demonstrated significant inverse relations between erythrocyte EPA + DHA levels (i.e. the Omega-3 Index) and total mortality. Recent data from the Cardiovascular Health Study reported the same relations between plasma phospholipid n-3 levels and overall healthy ageing. As regards randomised trials, studies in the 1990s and early 2000s were generally supportive of a cardiovascular benefit for fish oils (which contain EPA + DHA), but later trials were generally not able to duplicate these findings, at least for total CVD events. However, when restricted to effects on risk for fatal events, meta-analyses have shown consistent benefits for n-3 treatment. Taken together, the evidence is strong for a cardioprotective effect of EPA + DHA, especially when consumed in sufficient amounts to raise blood levels into healthy ranges. Establishing target EPA + DHA intakes to reduce risk for cardiovascular death is a high priority.

The effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study was carried out to evaluate the effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in diabetic people with coronary heart disease (CHD). METHODS: This randomized, double-blind, placebo-controlled trial was carried out among 60 diabetic people with CHD, aged 45-85 years old. Subjects were randomly allocated into two groups to receive either 50,000 IU vitamin D every 2 weeks plus 8 × 109 CFU/g probiotic of Lactocare Zisttakhmir Co (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at baseline and after the 12-week intervention to determine metabolic profiles. RESULTS: After the 12-week intervention, compared with the placebo, vitamin D and probiotic co-supplementation resulted in significant improvements in beck depression inventory total score (-2.8 ±â€¯3.8 vs. -0.9 ±â€¯2.1, P = 0.01), beck anxiety inventory scores (-2.1 ±â€¯2.3 vs. -0.8 ±â€¯1.4, P = 0.009) and general health questionnaire scores (-3.9 ±â€¯4.1 vs. -1.1 ±â€¯3.4, P = 0.005). Compared with the placebo, vitamin D and probiotic co-supplementation resulted in significant reductions in serum insulin levels (-2.8 ±â€¯3.8 vs. +0.2 ±â€¯4.9 µIU/mL, P = 0.009), homeostasis model of assessment-estimated insulin resistance (-1.0 ±â€¯1.6 vs. -0.1 ±â€¯1.5, P = 0.02), and a significant increase in serum 25-OH-vitamin D (+11.8 ±â€¯5.9 vs. +0.1 ±â€¯1.4 ng/mL, P < 0.001), the quantitative insulin sensitivity check index (+0.03 ±â€¯0.04 vs. -0.001 ±â€¯0.01, P = 0.003) and serum HDL-cholesterol levels (+2.3 ±â€¯3.5 vs. -0.5 ±â€¯3.8 mg/dL, P = 0.004). In addition, changes in serum high sensitivity C-reactive protein (hs-CRP) (-950.0 ±â€¯1811.2 vs. +260.5 ±â€¯2298.2 ng/mL, P = 0.02), plasma nitric oxide (NO) (+1.7 ±â€¯4.0 vs. -1.4 ±â€¯6.7 µmol/L, P = 0.03) and plasma total antioxidant capacity (TAC) (+12.6 ±â€¯41.6 vs. -116.9 ±â€¯324.2 mmol/L, P = 0.03) in the supplemented group were significantly different from the changes in these indicators in the placebo group. CONCLUSIONS: Overall, vitamin D and probiotic co-supplementation after 12 weeks among diabetic people with CHD had beneficial effects on mental health parameters, serum hs-CRP, plasma NO, TAC, glycemic control and HDL-cholesterol levels. CLINICAL TRIAL REGISTRATION NUMBER: http://www.irct.ir: IRCT2017073033941N4.

Recent Science and Clinical Application of Nutrition to Coronary Heart Disease.

One of the greatest threats to mortality in industrialized societies continues to be coronary heart disease (CHD). Moreover, the ability to decrease the incidence of CHD has reached a limit utilizing traditional diagnostic evaluations and prevention and treatment strategies for the top five cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking). It is well known that about 80% of CHD can be prevented with optimal nutrition, coupled with exercise, weight management, mild alcohol intake, and smoking cessation. Among all of these factors, optimal nutrition provides the basic foundation for prevention and treatment of CHD. Numerous prospective nutrition clinical trials have shown dramatic reductions in the incidence of CHD. As nutritional science and nutrigenomics research continues, our ability to adjust the best nutrition with an individualized approach is emerging. This article reviews the role of nutrition in the prevention and treatment of CHD and myocardial infarction (MI).

Flaxseed Oil Supplementation Improve Gene Expression Levels of PPAR-γ, LP(a), IL-1 and TNF-α in Type 2 Diabetic Patients with Coronary Heart Disease.

This study was carried out to determine the effects of flaxseed oil administration on gene expression levels related to insulin, lipid and inflammation in overweight diabetic patients with coronary heart disease (CHD). This randomized double-blind, placebo-controlled trial was conducted among 60 diabetic patients with CHD. Subjects were randomly allocated into two groups to intake either 1000 mg n-3 fatty acid from flaxseed oil containing 400 mg α-Linolenic acid [ALA (18:3n-3)] (n = 30) or placebo (n = 30) twice a day for 12 weeks. Gene expression related to insulin, lipid and inflammation were quantified in peripheral blood mononuclear cells (PBMC) of diabetic patients with CHD with RT-PCR method. Results of RT-PCR demonstrated that after the 12-week intervention, compared with the placebo, flaxseed oil supplementation could up-regulate gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.02) in PBMC of diabetic patients with CHD. In addition, compared with the placebo, taking flaxseed oil supplements down-regulated gene expression levels of lipoprotein(a) [LP(a)] (P = 0.001), interleukin-1 (IL-1) (P = 0.001) and tumor necrosis factor alpha (TNF-α) (P = 0.02) in PBMC of diabetic patients with CHD. We did not observe any significant effect of flaxseed oil supplementation on gene expression levels of low-density lipoprotein receptor (LDLR), IL-8 and transforming growth factor beta (TGF-ß) in PBMC of diabetic patients with CHD. Overall, flaxseed oil supplementation for 12 weeks in diabetic patients with CHD significantly improved gene expression levels of PPAR-γ, LP(a), IL-1 and TNF-α, but did not influence LDLR, IL-8 and TGF-ß.

Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73).

OBJECTIVE: To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis. DESIGN: The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted. SETTING: One nursing home and six state mental hospitals in Minnesota, United States. PARTICIPANTS: Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files. INTERVENTIONS: Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings. MAIN OUTCOME MEASURES: Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy. RESULTS: The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline -13.8%v-1.0%; P<0.001). Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup. There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001). There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts. Systematic review identified five randomized controlled trials for inclusion (n=10,808). In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27). CONCLUSIONS: Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.

A coconut extra virgin oil-rich diet increases HDL cholesterol and decreases waist circumference and body mass in coronary artery disease patients / El aceite de coco virgen extra rico en ácidos grasos incrementa el colesterol HDL y disminuye la circunferencia de la cintura y la masa corporal en pacientes con enfermedades de la arteria coronaria

Introduction: saturated fat restriction has been recommended for coronary arterial disease, but the role of coconut oil (Cocos nucifera L.) extra virgin, lauric acid source in the management of lipid profile remains unclear. Objective: to evaluate the effect of nutritional treatment associated with the consumption of extra virgin coconut oil in anthropometric parameters and lipid profile. Methods: we conducted a longitudinal study of 116 adults of both sexes presenting CAD. Patients were followed in two stages: the first stage (basal-3 months), intensive nutritional treatment. In the second stage (3-6 months), the subjects were divided into two groups: diet group associated with extra virgin coconut oil consumption (GDOC) and diet group (DG). Held monthly anthropometric measurements: body mass, waist circumference (WC), neck circumference (PP), body mass index (BMI). Gauged to collected blood pressure and blood samples were fasted for 12 hours, for total cholesterol analysis and fractions apoproteins (Apo A-1 and B), glucose, glycated hemoglobin (HbA1C), insulin (I). Comparing the averages at the beginning and end of the study employing the paired Student t-independent. And set the diastolic blood pressure by BMI using ANOVA. Analyses were performed using the SPSS statistical package, being significant p < 0.05. Results: the mean age of the population was 62.4 ± 7.7 years, 63.2% male, 70% elderly, 77.6% infarcted, 52.6% with angina, hypertension and dyslipidemia 100%. In the first stage the nutritional treatment reduced body weight, WC, BMI and PP and insulin concentrations, HbA1C, HOMA-IR and QUICK, without changing the other parameters. In the second stage of the study, it was observed that the GDOC maintained the reduction of body mass, BMI, WC, with a significant difference between groups for DC (-2.1 ± 2,7cm; p < 0.01). In addition, there was an increase in HDL-C concentrations, Apo A, with significant difference in GD, only for HDL-C (3.1 ± 7.4 mg/dL; p = 0.02). Conclusion: it was observed that the nutritional treatment associated with extra virgin coconut oil consumption reduced the CC and increased HDL-C levels in patients with CAD (AU)

Introducción: el aceite de coco (Cocos nucifera L.) virgen extra contiene una alta proporción de ácidos grasos de cadena media que parecen contribuir a la reducción del peso y podría ayudar en la prevención secundaria de la enfermedad arterial coronaria (EAC). Objetivo: evaluar el efecto del tratamiento nutricional asociado con el consumo de aceite de coco virgen extra en los parámetros antropométricos y el perfil lipídico. Métodos: se realizó un estudio longitudinal de 116 adultos de ambos sexos que presentan CAD. Los pacientes fueron seguidos en dos etapas: en la primera etapa (basal-3 meses), se llevó a cabo un tratamiento nutricional intensivo. En la segunda etapa (3-6 días), los sujetos fueron divididos en dos grupos: grupo asociado con el consumo de aceite extra virgen de coco (GDOC) y el grupo de dieta (GD). Se realizaron mediciones mensuales antropométricas: peso, circunferencia de la cintura (CC), circunferencia del cuello (PP) e índice de masa corporal (IMC). Se tomó la presión arterial y muestras de sangre recogidas en ayunas durante 12 horas para el análisis de colesterol total y lipoproteínas, apoproteínas (Apo A-1 y B), glucosa, hemoglobina glucosilada (HbA1c) e insulina (I). Se compararon los promedios al principio y al final del estudio mediante el test t de Student-independiente. Se ajustó la presión arterial diastólica por el IMC mediante ANOVA. Los análisis se realizaron con el paquete estadístico SPSS, siendo significativa p < 0.05. Resultados: la edad media de la población fue de 62,4 ± 7,7 años, el 63,2% hombres, 70% mayores, el 77,6% con infarto de miocardio, el 52,6% con angina de pecho y el 100% con hipertensión arterial y dislipidemia. En la primera etapa del tratamiento nutricional se redujeron las concentraciones de insulina, peso, WC, IMC y PP, HbA1C, HOMA-IR y rápido, sin cambiar otros parámetros. En la segunda etapa del estudio se observó que la GDOC mantiene la reducción del peso, BMI, WC, con una diferencia significativa entre los grupos para DC (-2,1 ± 2,7 cm; p < 0,01). Además, se produjo un aumento en las concentraciones de HDL-C, Apo A, con una diferencia significativa en GD, solo para HDL-C (3,1 ± 7,4 mg/dl; p = 0,02). Conclusión: se observó que el tratamiento nutricional asociado con el consumo de aceite de coco virgen extra redujo la CC e incrementó los niveles de HDL-C en pacientes con CAD (AU)

Palm oil and blood lipid-related markers of cardiovascular disease: a systematic review and meta-analysis of dietary intervention trials.

BACKGROUND: Palm oil (PO) may be an unhealthy fat because of its high saturated fatty acid content. OBJECTIVE: The objective was to assess the effect of substituting PO for other primary dietary fats on blood lipid-related markers of coronary heart disease (CHD) and cardiovascular disease (CVD). DESIGN: We performed a systematic review and meta-analysis of dietary intervention trials. Studies were eligible if they included original data comparing PO-rich diets with other fat-rich diets and analyzed at least one of the following CHD/CVD biomarkers: total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, TC/HDL cholesterol, LDL cholesterol/HDL cholesterol, triacylglycerols, apolipoprotein A-I and B, very-low-density lipoprotein cholesterol, and lipoprotein(a). RESULTS: Fifty-one studies were included. Intervention times ranged from 2 to 16 wk, and different fat substitutions ranged from 4% to 43%. Comparison of PO diets with diets rich in stearic acid, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) showed significantly higher TC, LDL cholesterol, apolipoprotein B, HDL cholesterol, and apolipoprotein A-I, whereas most of the same biomarkers were significantly lower when compared with diets rich in myristic/lauric acid. Comparison of PO-rich diets with diets rich in trans fatty acids showed significantly higher concentrations of HDL cholesterol and apolipoprotein A-I and significantly lower apolipoprotein B, triacylglycerols, and TC/HDL cholesterol. Stratified and meta-regression analyses showed that the higher concentrations of TC and LDL cholesterol, when PO was substituted for MUFAs and PUFAs, were not significant in young people and in subjects with diets with a lower percentage of energy from fat. CONCLUSIONS: Both favorable and unfavorable changes in CHD/CVD risk markers occurred when PO was substituted for the primary dietary fats, whereas only favorable changes occurred when PO was substituted for trans fatty acids. Additional studies are needed to provide guidance for policymaking.

Protective effects of sea spaghetti-enriched restructured pork against dietary cholesterol: effects on arylesterase and lipoprotein profile and composition of growing rats.

There is a general assumption that seaweeds are hypocholesterolemics and antioxidants. However, controversial results suggest specific properties for each individual alga. This study aims to assess the effect of including Sea Spaghetti alga (S) in a restructured-pork (RP) diet, both enriched and not enriched with dietary cholesterol, on arylesterase (AE) activity and lipoprotein concentration and composition of Wistar rats. Four groups of 10 growing male Wistar rats were each fed a mix of 85% AIN-93M diet and 15% freeze-dried RP for 5 weeks. The control group (C) consumed control RP-C; the S group consumed RP-S with 5% seaweeds; the Chol-C group consumed the C diet but enriched with cholesterol (2.43%) and cholic acid (0.49%); the Chol-S group consumed the S diet but enriched with cholesterol and cholic acid. AE activity was five times higher (P<.01) in S compared with C rats, but three times lower in Chol-S compared with Chol-C rats (P<.01). The Chol-C diet induced hypercholesterolemia but reduced triglycerides (TG), giving rise to the presence of very low-density lipoprotein (VLDL) that was enriched in cholesterol. The Chol-S diet partially blocked (P<.001) the hypercholesterolemic induction of the Chol-C diet, and reduced TG levels (P<.05) with respect to S rats. The cholesterol supplementation increased total cholesterol, VLDL-cholesterol, and intermediate-density lipoprotein+LDL-cholesterol (IDL+LDL)-cholesterol (P<.001) in Chol-C rats, but the effect was lower in the Chol-S diet. In conclusion, RP-S increases the antioxidant capacity within a noncholesterol enriched diet while improving the lipoprotein profile within a cholesterol-enriched diet.

Diets to prevent coronary heart disease 1957-2013: what have we learned?

Our understanding of the potential cardioprotective properties of nutrition is relatively recent, with most relevant studies completed in the last several decades. During that time, there has been an evolution in the focus of nutritional intervention. Early trials emphasized reduction of dietary fat with the goal of preventing heart disease by reducing serum cholesterol. Results from trials focused exclusively on dietary fat reduction were disappointing, prompting subsequent studies incorporating a whole diet approach with a nuanced recommendation for fat intake. The Mediterranean-style diet, with a focus on vegetables, fruit, fish, whole grains, and olive oil, has proven to reduce cardiovascular events to a degree greater than low-fat diets and equal to or greater than the benefit observed in statin trials.

n-3 fatty acids: functional differences between food intake, oral supplementation and drug treatments.

n-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for mammalian cells that are not able to synthesise de novo their precursor, α-linolenic acid, and may only partially convert it to eicosapentaenoic acid (EPA) and to a very small extent to docosahexaenoic acid (DHA). For this reason, nutritional guidelines for cardiovascular prevention recommend regular fish consumption (approximately two portions per week) in order to increase the intake of the n-3 PUFAs EPA and DHA, mainly referring to fatty fish, living in cold waters, usually very rich in these fatty acids. However, the indication to consume fish regularly is unlikely to be sufficient to ensure that patients with documented coronary heart diseases receive the daily amount of EPA+DHA (ca. 1g) necessary for effective secondary prevention of the disease. This has prompted the development of pharmaceutical formulations both for dietary supplementation and for therapeutic administration, based on several dietary sources, containing greatly variable amounts of EPA and DHA, often with different availabilities. Critical knowledge of these characteristics allows the selection of the best approach in order to optimise the n-3 PUFA supply in various individuals.

Current evidence and future perspectives on n-3 PUFAs.

The family of polyunsaturated fatty acids (PUFAs), which can be found in most lipid classes, includes n-3 PUFAs essential for mammals and whose deficiency is associated with multiple diseases. Because of their multiple physiological actions, n-3 PUFAs play a crucial role in normal human metabolism as well as maintenance of a healthy status, with clinical effects that are not limited to the cardiovascular system but also include maternal and offspring health, growth and development, immune system disorders, cancer, cognitive function and psychological status. Multiple health organisations and scientific societies recommend increasing food-derived n-3 PUFA intake and also suggest that patients with documented coronary heart disease receive a minimum of 1000 mg/day of eicosapentaenoic acid and docosahexaenoic acid. The preventive and therapeutic effects of n-3 PUFAs appear to be largely dependent on the dosages employed and the characteristics of selected patients. So, in the era of personalised medicine, the time has come to move from generic advice to increase n-3 PUFA intake to a more evidence-based approach characterised by tailored indications to n-3 PUFA dietary or supplement consumption. This approach will require evaluation on a case-to-case basis the potential usefulness of n-3 PUFAs, taking into consideration their 'pleiotropic effects', the optimal dose for any given indication in relation to international guidelines, potential interactions with background therapy, possible side effects, differences in genetics and dietary response to supplementation, and the cost:benefit ratio, which is likely to vary as a function of differences in the range of fish intake in the diet.

Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis.

OBJECTIVE: To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death. DESIGN: Evaluation of recovered data from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73; and an updated meta-analysis including these previously missing data. SETTING: Ambulatory, coronary care clinic in Sydney, Australia. PARTICIPANTS: 458 men aged 30-59 years with a recent coronary event. INTERVENTIONS: Replacement of dietary saturated fats (from animal fats, common margarines, and shortenings) with omega 6 linoleic acid (from safflower oil and safflower oil polyunsaturated margarine). Controls received no specific dietary instruction or study foods. All non-dietary aspects were designed to be equivalent in both groups. OUTCOME MEASURES: All cause mortality (primary outcome), cardiovascular mortality, and mortality from coronary heart disease (secondary outcomes). We used an intention to treat, survival analysis approach to compare mortality outcomes by group. RESULTS: The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6% v 11.8%, hazard ratio 1.62 (95% confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04). Inclusion of these recovered data in an updated meta-analysis of linoleic acid intervention trials showed non-significant trends toward increased risks of death from coronary heart disease (hazard ratio 1.33 (0.99 to 1.79); P=0.06) and cardiovascular disease (1.27 (0.98 to 1.65); P=0.07). CONCLUSIONS: Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats. TRIAL REGISTRATION: Clinical trials NCT01621087.

Fatty acids in cardiovascular health and disease: a comprehensive update.

Research dating back to the 1950s reported an association between the consumption of saturated fatty acids (SFAs) and risk of coronary heart disease. Recent epidemiological evidence, however, challenges these findings. It is well accepted that the consumption of SFAs increases low-density lipoprotein cholesterol (LDL-C), whereas carbohydrates, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) do not. High-density lipoprotein (HDL)-C increases with SFA intake. Among individuals who are insulin resistant, a low-fat, high-carbohydrate diet typically has an adverse effect on lipid profiles (in addition to decreasing HDL-C, it also increases triglyceride and LDL particle concentrations). Consequently, a moderate fat diet in which unsaturated fatty acids replace SFAs and carbohydrates are not augmented is advised to lower LDL-C; compared with a low-fat diet, a moderate-fat diet will lower triglycerides and increase HDL-C. Now, there is some new evidence that is questioning the health benefits of even MUFAs and PUFAs. In addition, in a few recent studies investigators have also failed to demonstrate expected cardiovascular benefits of marine-derived omega-3 fatty acids. To clarify the clinical pros and cons of dietary fats, the National Lipid Association held a fatty acid symposium at the 2011 National Lipid Association Scientific Sessions. During these sessions, the science regarding the effects of different fatty acid classes on coronary heart disease risk was reviewed.

Dietary fats and coronary heart disease.

The relation of dietary fat to risk of coronary heart disease (CHD) has been studied extensively using many approaches, including controlled feeding studies with surrogate end-points such as plasma lipids, limited randomized trials and large cohort studies. All lines of evidence indicate that specific dietary fatty acids play important roles in the cause and the prevention of CHD, but total fat as a percent of energy is unimportant. Trans fatty acids from partially hydrogenated vegetable oils have clear adverse effects and should be eliminated. Modest reductions in CHD rates by further decreases in saturated fat are possible if saturated fat is replaced by a combination of poly- and mono-unsaturated fat, and the benefits of polyunsaturated fat appear strongest. However, little or no benefit is likely if saturated fat is replaced by carbohydrate, but this will in part depend on the form of carbohydrate. Because both N-6 and N-3 polyunsaturated fatty acids are essential and reduce risk of heart disease, the ratio of N-6 to N-3 is not useful and can be misleading. In practice, reducing red meat and dairy products in a food supply and increasing intakes of nuts, fish, soy products and nonhydrogenated vegetable oils will improve the mix of fatty acids and have a markedly beneficial effect on rates of CHD.